Effects of G-protein mutations on skin color

A new class of dominant dark skin ( Dsk ) mutations discovered in a screen of ∼30,000 mice is caused by increased dermal melanin. We identified three of four such mutations as hypermorphic alleles of Gnaq and Gna11 , which encode widely expressed Gαq subunits, act in an additive and quantitative manner, and require Ednrb . Interactions between Gq and Kit receptor tyrosine kinase signaling can mediate coordinate or independent control of skin and hair color. Our results provide a mechanism that can explain several aspects of human pigmentary variation and show how polymorphism of essential proteins and signaling pathways can affect a single physiologic system.